Quality of life and mental health in multiple sclerosis patients during the COVID-19 Pandemic

Abstract

Background

The COVID-19 pandemic had a profound impact on mental health symptoms and quality of life (QoL) in the general population due to necessary public health restrictions such as social distancing. The psychosocial effect of the pandemic on vulnerable groups such as people living with Multiple Sclerosis (PwMS) has been scarcely explored in countries with additional socioeconomical burdens such as access to healthcare disparities

Methods

A questionnaire exploring sociodemographic variables, quality of life, mental health determinants and sleep quality was applied to 92 PwMS to explore changes prior and during the pandemic regarding these domains

Results

58.8% of the subjects were female, median age was 37.1 (± 8.5) years and relapsing-remitting MS was the predominant clinical subtype (83.5%). Unemployment rate significantly increased during the pandemic (12.3% vs 27.8%; p= 0.001). Only 46.4% received medical follow-up care during the pandemic. QoL was affected predominantly due to limitations in instrumented activities of daily life (IADL). Neuropsychiatric symptoms, requiring healthcare during the pandemic, anxiety prior to the pandemic and restricted IADL were predictors of MS-related physical impact worsening, while decreased physical/emotional wellbeing selfcare, neuropsychiatric symptoms, bad sleep quality, anxiety prior to the pandemic and restricted non-instrumental ADL predicted aggravation of MS-related psychological impact measured by the MSIS-29. Curiously, specific items regarding anxiety were more prevalent prior to the pandemic (anxious mood; p=0.02, helplessness; p=0.01), sleep problems; p=0.001 and cardiovascular symptoms; p=0.001, nevertheless, stability was observed for most items. Importantly, 77.3% of PwMS reported at least one neuropsychiatric symptom

Conclusion

The deleterious effects of the COVID-19 pandemic on psychosocial wellbeing in PwMS, QoL and mental health outcomes are frequently overseen in vulnerable populations such as PwMS. Albeit the limitations of this study, our results may help implement policies that prevent negative outcomes on psychosocial wellbeing due to public health measures (e.g., social distancing) in MS and other neurological diseases that inexorably need constant follow-up.

Background

The COVID-19 pandemic was declared as a major public health threat by the World Health Organization on March 11^th, 2020. To contain contagion, governments implemented policies such as social distancing and mobility restrictions that impacted on activities of daily life and mental health of the general population. Consequently, decreased access to healthcare due to non-COVID-19 conditions resulted in excess morbidity and mortality (Ren and Guo., 2020).

Until April 2022, more than 630 million cases of SARS-CoV2 and more than 6.6 million COVID-19-related deaths have been reported. Neurological symptoms associated to mild COVID-19, include dizziness, headache, anosmia or ageusia (Mao et al., 2020). Furthermore, morbimortality of chronic neurological illnesses has been negatively impacted due to the limited access to follow-up and acute care (Matias-Guiu et al., 2021).

SARS-COV2 associated immune response dysregulation, characterized by systemic inflammation, cytokine expression and macrophage activation may lead to the pathological process known as secondary hemophagocytic lymphohistiocytosis, classically of subacute onset. Thus, para-infectious immunomodulated clinical syndromes typically occur after the acute phase of the disease. (Andalib et al., 2021).

Such process may increase the risk for symptom worsening or flaring-up in people living with autoimmune diseases such as Multiple Sclerosis (MS).

Hence, COVID-19 may negatively impact symptoms and disease characteristics of people living with MS (PwMS). Nonetheless the pandemic itself as a social phenomenon, could be related to deleterious outcomes in mental health, exacerbated by the lack of access to healthcare services, lack of medications and isolation.

Uncertainty and misinformation regarding contagions, vaccine side-effects, the use of immunotherapy and its interaction with MS treatments are known to increase MS-related worries (Morris-Bankole et al., 2021), representing an additional burden for PwMS.

Anxiety and depression are common in PwMS and have been reported to be as high as 57% and 40% respectively (Butler et al., 2016; Feinstein et al., 2014). The prevalence of anxiety is disproportionally higher in PwMS than in general population (Boeschoten et al., 2017). It has been observed that younger people with MS are more vulnerable to have anxiety related symptoms because of the pandemic (Radulovic et al., 2020). Affective symptoms in PwMS correlate with worse quality of life (QoL), higher fatigue and disability scores and a more aggressive MS progression (Patel et al., 2018). Furthermore, an increased severity of self-perceived symptoms and worse treatment adherence have been reported (Mohr and Cox, 2001).

It is known that PwMS develop maladaptive coping strategies that make them more susceptible to neuropsychiatric illness (Amato et al., 2019). Up to 93% of the countries affected by the pandemic have reported an increased need for emotional support services (Pandey et al., 2021).

To date, no study has addressed the effect of the COVID-19 pandemic on QoL and mental health in PwMS in Mexican population. Hence, this study attempts to describe the relation of the COVID-19 pandemic with QoL, mental health and access to healthcare in Mexican PwMS.

Methods

Information of 142 PwMS, who are followed up regularly in the MS Clinic of the National Institute of Neurology and Neurosurgery in Mexico City (NINN) was recollected from November to December 2021. Telephone or e-mail contact was possible for 97 patients, who were invited to participate voluntarily in a transversal study regarding the impact of COVID19 pandemic on QoL and emotional state.

The following criteria were considered for the selection of patients.

Inclusion criteria: Mexican patients under 60 years of with ≥5 years with the diagnosis of MS. Exclusion criteria: patients over 60 years of age, impediments to answering the online questionnaire and low level of education.

An online Google Forms questionnaire was applied. Patients were contacted by phone to explain the purpose of the study. Subsequently, the questionnaire was sent by e-mail. The study was previously approved by the Institutional Review Board (IRB) of the NINN. All participants filled and signed an electronic consent form prior to questionnaire response.

Table 1 shows the scales and items included in the online questionnaire.

Table 1.

Self-reported assessments used for the evaluation of QoL and mental health in PwEM during the COVID-19 pandemic.

Area	Questionnaire	Reactives (α)	Domain	Author
Context of the disease during the COVID-19 pandemic	Demographic.	5	Characteristics of PwMS (age, education, gender, etc.).	Own elaboration.
	Clinical features of PwMS.	3	- MS Subtype. - Time of diagnosis. - Comorbidities.	Own elaboration.
	Healthcare access and follow-up during the COVID-19 pandemic.	8	- Treatment. - In-patient consultations. - MS-relapses. - COVID-19 symptoms. - Vaccination status. - Healthcare satisfaction. - Physical and emotional wellbeing care. - General health perception.	Own elaboration.
Quality of life	Barthel Index (ADL).	11 (0.88)	- Activities of daily life (prior and during the pandemic).	Mahoney & Barthel (1965)
	Lawton & Brody Scale (IADL).	8 (0.94)	- Instrumented activities of daily life (prior and during the pandemic).	Trigás-Ferrín et al. (2011)
	Multiple Sclerosis Impact Scale (MSIS-29).	29 (0.93)	- Physical impact. - Psychological impact.	Hobart et al. (2001)
Mental health	Patient Health Questionnaire for Depression (PHQ-9).	9 (0.89)	- Affective Symptoms. - Somatic Symptoms.	Spitzer et al. (1999), Familiar et al. (2015)
	Hamilton Anxiety Scale.	14 (0.89)	- Anxiety (prior and during the pandemic).	Hamilton (1959),Lobo et al. (2002)
	Neuropsychiatric Inventory (NPI).	16 (0.67)	- Behavioral symptoms.	Cummings et al. (1994)
Sleep	The Pittsburgh Sleep Quality Index (PSQI).	6 (0.78)	- Quality of Sleep.	Jiménez-Genchi et al. (2008)

Statistical analysis

Descriptive statistics were performed for sociodemographic and clinical variables. Mann-Whitney U test was performed to assess the relationship between MSIS-29, PHQ-9 and Anxiety scores with clinical and sociodemographic variables. Spearman correlation was used to evaluate the relationship between continuous variables.

Multiple regression models were used to determine the association between significative variables of prior analysis with MSIS-29 (psychological and physical domains), PHQ-9 (affective and somatic domains) and Hamilton Anxiety Scale scores. SPSSv23 statistics software was used.

Results

Clinical and sociodemographic characteristics

58.8% of all 97 evaluated PwMS were female, median age was 37.1 (± 8.5) years, 64.9% had graduate or postgraduate education, 48.5% lived with family and 33% with their couple. Prior to the COVID-19 pandemic 45 individuals (46.6%) were involved in an economic activity (26.8% were employed, 10.3% were self-employed and 9.3% were informal merchants). Regarding clinical characteristics, mean time of diagnosis was 8.5 (± 6.5) years and the predominant MS subtype was relapsing-remitting MS (83.5%). See Table 2 .

Table 2.

Clinical and demographical characteristics.

Variable	Category	Frequency (%)
Sex	Female Male	57 (58.8) 40 (41.2)
Age	Years [M (±DS); R: 21-58]	37.1 (8.5)
Time of Diagnosis	Years [M (±DS); R: 1987-2020]	8.2 (6.5)
EDSS	Score [M (±DS); R: 0-8]	2.5 (1.99)
Education	Elementary school Middle school High school Graduate Postgraduate	2 (2.1) 6 (6.2) 26 (26.8) 50 (51.5) 13 (13.4)
Occupation	Employed Informal merchant Self-Employed Student Domestic work Unemployed Did not respond	26 (26.8) 9 (9.3) 10 (10.3) 12 (12.4) 18 (18.6) 16 (16.5) 6 (6.2)
Lives with	Parents Spouse Offspring Siblings Uncle/Aunt Friend/Neighbor Alone Grandparents	47 (48.5) 32 (33.0) 3 (3.1) 5 (5.2) 1 (1.0) 4 (4.1) 3 (3.1) 1 (1.0)
Clinical Subtype	RRMS SPMS PPMS	81 (83.5) 7 (7.2) 6 (6.2)
Comorbidity	Diabetes Mellitus Hypertension Others None	1 (1.0) 6 (6.2) 6 (6.2) 65 (67.0)

RRMS; Relapsing-Remitting Multiple Sclerosis. SPMS; Secondary Progressive Multiple Sclerosis. PPMS; Primary Progressive Multiple Sclerosis.

PwMS have reported higher unemployment during the COVID-19 pandemic

(Shang, 2020). Table 3 shows the trends of occupation activity of PwMS during the pandemic. A significant proportion of PwMS stopped their economic activities or studies and became unemployed.

Table 3.

Trends of occupation of PwMS during the Covid-19 pandemic.

Occupation	Prior to pandemic		During the pandemic
	F n(%)	M n(%)	F n(%)	M n(%)	Value p
Employed	7 (13.7)	19 (47.5)	5 (9.8)	11 (27.5)	0.001
Informal merchant	5 (9.8)	4 (10.0)	3 (5.9)	1 (2.5)
Self-employed	6 (11.8)	4 (10.0)	7 (13.7)	5 (12.5)
Student	8 (15.7)	4 (10.0)	6 (11.8)	2 (5.0)
Domestic work	13 (25.5)	5 (12.5)	18 (35.3)	6 (15.0)
Unemployed	12 (23.5)	4 (10.0)	12 (23.5)	15 (37.5)

Data Missing (6). F; Female. M; Male.

Healthcare access and follow-up during the COVID-19 pandemic in PwMS

23.7% of our sample underwent change of MS medical treatment, 17.5% reported stopping their treatment due to shortage of supplies and 18.6% reported not having any treatment at all. 46.4% received medical care during the pandemic and 24.7% stopped going to appointments due to fear of contagion. In 21 cases, consultations were due to suspicion of relapses and 6 patients required hospitalization during the pandemic. 49.5% reported a good satisfaction with healthcare during the pandemic, 28.9% regular satisfaction and 13.4% were unsatisfied.

17.5% of PwMS went to consultations due to COVID-19 symptoms (4 had positive COVID-19 test result, 3 had a family member with a positive result and 8 did not have diagnostic testing performed). 71.1% had a full vaccination schedule, 15.5% had an incomplete schedule and 7.2% was not vaccinated, the rest did not respond. Self-perception of health was overall good in 41.2% and regular to bad in 57.5%.

Quality of life

Differences were observed when comparing ADL prior and during the pandemic. Activities that showed statistically significant differences were fundamentally IADL such as buying things (82.5 vs 69.1; p=0.02), managing money (82.5 vs 75.3; p=0.01) and using transportation (72.2 vs 48.5; p=0.001). The MSIS-29 is a nominal continuous scale (0 to 100) that correlates directly to the physical and psychological impact of MS. A mean score of 19.02 (±19.38) for physical impact, 24.05 (±21.82) for psychological impact and mean total score of 43.07 (±38.26) were obtained.

Mental Health

According to the PHQ-9 results, 38.1% of PwMS expressed mild depressive symptoms, 19.6% moderate depression and 1% severe depression. We observed differences in anxiety measured by The Hamilton Anxiety Scale prior and during the pandemic in specific items: anxious mood (77.3 vs 66.0; p=0.02), helplessness (68.0 vs 54.3; p=0.01), sleep problems (75.3 vs 57.7; p=0.001) and cardiovascular symptoms (91.8 vs 62.9; p=0.001).

In terms of sleep quality during the pandemic, 46.4% of PwMS reported bad sleep quality per the PSQI score.

The mean NPI score in PwMS during the pandemic was 6.01 (±7.2). 77.3% reported any psychiatric symptom, more frequently anxiety (56.7%), depression (52.6%), apathy (48.5%) and irritability (46.4%).

Table 4 summarizes our findings on the impact of the COVID-19 pandemic on QoL (MSIS-29), depressive symptoms (PHQ-9) and anxiety (Hamilton Anxiety Scale) and their association to predictive variables.

Table 4.

Multiple Regression Model for QoL (MSIS-29,) Depression (PHQ-9) and Anxiety (Hamilton Anxiety Scale) in PwMS during the pandemic.

Variables	MSIS-29-Phy			MSIS-29-Psy			PHQ-Affective			PHQ-Somatic			Anxiety
	b	F	p	b	F	p	b	F	p	b	F	p	b	F	p
Education	-	-	-	-	-	-	-	-	-	-0.217	-2.900	0.054	-	-	-
Do you take care of your physical/emotional wellbeing?	0.169	1.837	0.070	0.161	2.256	0.027	-	-	-	-	-	-	0.244	2.444	0.017
Have you required healthcare during the pandemic?	-0.208	-2.412	0.018	-0.126	-1.739	0.086	-	-	-	-	-	-	-	-	-
Have you required healthcare due to relapses of the disease?	-	-	-	-	-	-	0.218	2.335	0.022	-	-	-	-	-	-
Neuropsychiatric Inventory	0.350	3.538	0.001	0.314	3.781	0.001	0.418	4.533	0.001	0.164	2.028	0.046	-	-	-
Bad Sleep Quality (PSQI)	-	-	-	0.322	4.239	0.001	-	-	-	0.473	6.144	0.001	0.432	4.291	0.001
Anxiety prior to the pandemic	-0.352	-3.989	0.001	0.315	4.013	0.001	0.330	3.774	0.001	0.348	4.576	0.001	-	-	-
ADL	-	-	-	0.154	2.133	0.036	-	-	-	-	-	-	-	-	-
IADL	0.284	3.053	0.003	-	-	-	-	-	-	-	-	-	-	-	-

MSIS-29-Phy; Multiple Sclerosis Physical Impact Scale. MSIS-29-Psy; Multiple Sclerosis Psychological Impact Scale. PHQ-Affective; Patient Health Questionnaire- Affective. PHQ-Somatic; Patient Health Questionnaire- Somatic. PSQI; Pittsburgh Sleep Quality Index. ADL; Activities of Daily Living. IADL; Instrumental Activities of Daily Living. Only statistically significant or with statistical tendency variables are shown.

Predictors of physical impact in PwMS include requiring healthcare during the pandemic, the presence of neuropsychiatric symptoms (NPI), presence of anxiety symptoms prior to the pandemic and worsening of IADL during the pandemic.

Predictors of psychological impact in PwMS are related to physical/emotional wellbeing care, neuropsychiatric symptoms, bad sleep quality, presence of anxiety symptoms prior to the pandemic and worsening of ADL during the pandemic.

Regarding the perception of affective health in PwMS, predictors include relapses of the disease, neuropsychiatric symptoms and anxiety prior to the pandemic. On the other hand, predictors for worsening perception of somatic health are related to education level, neuropsychiatric symptoms, bad sleep quality and anxiety prior to the pandemic. Lastly, symptoms of anxiety are related to bad sleep quality and physical/emotional wellbeing care.

Discussion

This study describes the relationship between the COVID-19 pandemic and several determinants of QoL, mental health and access to healthcare in PwMS. The COVID-19 pandemic has gravely impacted wellbeing and mental health in people around the globe. The effect of the pandemic on PwMS has been reported in various studies. We emphasize the importance of revising the social factors that impact health in people during challenging times such as viral pandemics.

Most of our sample consisted of young productive women with a mean age of 37.1 years, who had deleterious consequences in their work life, with a significant increase of unemployment prior to and during the pandemic (16.5% vs 27.8%), phenomenon that has been observed in other countries such as China (44.4.%) and Spain (30.7%) (Shang, 2020). It is worth mentioning that albeit not explored in detail, the increment of unemployment in vulnerable groups is associated with an increase of domestic abuse, and PwMS are indeed a vulnerable and susceptible demographic group (Lawson et al, 2020).

A high percentage of the interviewed PwMS (24%) stopped going to medical appointments due to fear of contagion. It is known that COVID-19 contagion preoccupation impact on MS-related worries (Pandey et al., 2021).

Furthermore, unfiltered, and widely distributed misinformation regarding the use and effects of vaccination, sparked skepticism and contributed to the excess of depression and anxiety (Tai et al., 2021). Nevertheless, we found that 86% of our sample had been vaccinated against SARS-CoV2 virus, 71% with a full schedule and 15% with one dose. This suggests that despite the flow of misleading information regarding vaccines, PwMS opt to obtain it.

We found that 57% of PwMS classify their overall health status as regular to bad. In this regard, a negative self-reported health status is associated to worse outcomes on psychological wellbeing, anxiety and depression due to the pandemic (Wang et al., 2020).

Even though we observed higher scores of anxiety prior to the pandemic in PwMS, mainly in items that evaluate anxious mood, helplessness, sleep problems and cardiovascular symptoms, overall anxiety was still present during the pandemic. We found that 77.3% of PwMS report at least one neuropsychiatric symptom, more frequently depression, anxiety, apathy and irritability. These symptoms may be related to lifestyle changes and isolation due to social distancing and restrictions associated to the pandemic.

We found predictors for psychological and physical impact, and QoL that are related to neuropsychiatric symptoms during the COVID-19 pandemic. Physical impact predictors are related to IADL and healthcare, while psychological impact predictors are more related to basic ADL, care of physical and emotional wellbeing and sleep quality.

MS specialists should address and develop strategies to successfully monitor PwMS for neuropsychiatric complications, IADL and ADL and sleep quality, all of which affect QoL negatively. We emphasize on the importance of addressing neuropsychiatric symptoms in PwMS, especially during challenging circumstances such as viral outbreaks.

Most PwMS receive immunosuppressant or immunomodulatory therapies, and thus, represent, in theory, a high-risk population in viral pandemics and may have a higher related mental health burden. The COVID-19 pandemic has sparked worry and preoccupation in PwMS and other autoimmune conditions due to a higher risk of infection or worse outcomes of the disease (Bachiller-Corral et al., 2021). Furthermore, public health policies implemented to contain the disease's dissemination have impaired the access to specialized healthcare and follow-up in most PwMS (Moss et al., 2020).

According to the WHO, social determinants of access and quality of healthcare include the geographical place of birth of a population and the intrinsic challenges and disparities of the region (Bernardini et al, 2021). Vulnerable groups, such as PwMS, paired with healthcare disparities in the developing world, increase the incidence of stress, anxiety and depression, this fact helps to understand the impact of social determinants on neuropsychiatric symptoms (Macias Gil, et al, 2021). The WHO Member States have emphasized the importance of expanding mental health services and psychosocial support networks as fundamental components of the universal sanitary coverage.

Limitations of the study include a relatively small simple. Further studies with a prolonged follow-up of PwMS after the pandemic may be needed to better understand the psychosocial outcomes found in our study.

Conclusion

The observed results may help implement policies that prevent negative outcomes on psychosocial wellbeing because of public health measures (e.g., social distancing) in this and other neurological diseases that inexorably need constant follow-up. It is necessary to develop flexible and efficacious strategies that facilitate patient care in conditions of increased vulnerability.

Credit author statement

Yaneth Rodriguez-Agudelo: Conceptualisation, methodology, research and writing original draft.

Jaqueline Nava-Adan: Methodology, research and writing original draft.

Francisco Paz-Rodriguez: Research, formal analysis and writing original draft.

Arturo Abundes-Corona: Review, editing and translation to English.

Jose Flores-Rivera: Review and editing.

Teresa Corona-Vásquez: Conceptualisation, writing, review, editing and supervision.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.